Intracellular molecular signaling networks communicate via kinases that phosphorylate target substrates to regulate critical aspects of growth and survival. PIM-1, a proto-oncogenic serine/threonine kinase, was originally discovered as the proviral integration site for Moloney murine Leukemia virus. PIM-1 is up-regulated in prostate cancer. The gene is highly expressed in the liver and spleen during fetal hematopoiesis and primarily in B-lymphoid and myeloid cell lines.
PIM-1 exists in two isoforms with molecular weights of 34 and 44 kDa. The 34 kDa isoform is cytosolic and nuclear localized, while the 44 kDa isoform was recently found to be membrane bound. PIM-1 may be a relatively promiscuous kinase based upon minimal target substrate recognition sequence requirements and capacity for autophosphorylation. Two additional family members, PIM-2 and PIM-3, may exhibit functional redundancy with PIM-1.
Induction of PIM-1 expression is mediated by cytokines and growth factors including LIF, GM-CSF, EGF, and most interleukins, consistent with a role for PIM-1 in proliferation and survival of hematopoeitic cells. PIM-1 mediates proliferative actions through phosphorylation of multiple target substrates, resulting in cell cycle transition, as well as protective effects via phosphorylation of multiple targets. Induction of PIM-1 expression has been linked to AKT (a serine/threonine kinase) in hematopoeitic cells.